Lipid peroxidation and protein oxidation in patients affected by Hodgkin's lymphoma.

A dysregulation of the redox homoeostasis has been reported in various neoplastic disorders. Malondialdehyde/4-hydroxy-2,3-nonenal (MDA/HNE) and protein carbonyl groups represent in vivo indexes of lipid peroxidation and protein oxidation, respectively, suitable to investigate radical-mediated physio-pathological conditions. We evaluated MDA/HNE and protein carbonyl groups in sera of untreated Hodgkin's lymphoma (HL) patients in advanced disease stages, in order to quantify the oxidative stress. HL patients displayed significantly higher levels of both MDA/HNE and protein carbonyl groups as compared with healthy controls. This is the first evidence that a strong increase in HL is one of the most common haematological malignancies, representing approximately 30% of all lymphomas in the circulating protein carbonyl content in HL. These findings may contribute to a better definition of the redox homoeostasis dysregulation in HL

Retrospective analysis of mantle cell lymphoma: experience of the Gruppo Italiano per lo Studio dei Linfomi (GISL)

Background and Objective. Mantle cell lymphoma is a recently recognized histologic entity with specific biological and clinical features. Clinically, the reported unfavorable outcome of these patients has focused attention on this category of non-Hodgkin's lymphoma (NHL). Design and Methods. The slide specimens of 69 NHL patients, originally classified as Working Formulation (WF) group B and E, were reviewed. The clinical features at presentation, response to therapy, response duration and survival were analyzed in cases reclassified as MCL. The correlation between clinical and histologic characteristics and the final outcome was evaluated. Results. Out of 69 cases, 34 specimens were reclassified as MCL; in 6 patients, previously classified as WF group B, the nodular pattern was confirmed; in 2 instances the blastoid form was recognized. After a median follow-up of 35.7 months, the entire series displayed a median overall survival of 41.2 months; a significantly longer survival was associated with the nodular histologic pattern, IPI score <2, response achievement, and a higher Hb level. The vast majority of patients received anthracycline-containing combination chemotherapy. Complete remission rate was 38.8% and overall response rate was 67.6%; response achievement was significantly influenced only by Hb level. Median response duration was 23.3 months. Interpretation and Conclusions. The present study confirms the unfavorable clinical course of MCL and the possible need for an alternative therapeutic strategy for this NHL category. Therefore, the correct identification of MCL at diagnosis appears of relevance. (C)1998, Ferrata Storti Foundation

Weekly administration of vincristine, cyclophosphamide, mitoxantrone and bleomycin (VEMB) in the treatment of elderly aggressive non Hodgkin's lymphoma

Background and Objective. Aim of the study was to assess the efficacy of VEMB, a short-lasting therapeutic regimen (50 days) which alternates two myelotoxic drugs (cyclophosphamide and mitoxantrone) every week with two less hematologically toxic drugs (vincristine and bleomycin) in the treatment of aggressive NHL in the elderly (over 70). Design and Methods. Between November 1994 and March 1996, 37 patients aged more than 70 years, with highly or moderately malignant NHL (according to the Working Formulation) have been enrolled into the study. The stage of the disease ranged between II and IV according to Ann Arbor. Mean age was 77 years; 14 patients (38%) had stage IV; 19 patients (51%) had LDH higher than normal; 26 patients (70%) had extranodal and 9 patients (24%) had bulky disease at time of diagnosis. Results. Sixty-two percent of patients achieved a complete and 22% a partial remission. Non-responders amounted to 5%. Four patients (11%) died during the therapy; Nine patients (24%) experienced grade III-IV neutropenia. The most frequently observed event was mild neurotoxicity (43% of cases). The overall survival rate at 30 months was 55%. DFS at 24 months was 66%. Interpretation and Conclusions. VEMB is a therapeutic regimen whose efficacy is comparable to that of the other derived MACOP-B therapeutic regimens used in the elderly NHL. It has proved to have a good feasibility, though the number of toxic deaths should not be neglected

Clinical relevance of immunophenotype in a retrospective comparative study of 297 peripheral T-cell lymphomas, unspecified, and 496 diffuse large B-cell lymphomas: experience of the Intergruppo Italiano Linformi.

BACKGROUND. To assess the impact of T-cell/B-cell phenotype on clinical outcome, the authors retrospectively compared patients who had peripheral T-cell lymphoma, unspecified (PTCL-U), with patients who had diffuse large B-cell lymphoma (DLBCL). METHODS. Two hundred ninety-seven cases of PTCL-U and 496 cases of DLBCL that had been transferred from the files of the Intergruppo Italiano Linfomi or the Gruppo Italiano Linfomi were integrated into a unique working file and reviewed by the authors. RESULTS. The PTCL-U group and the DLBCL group had significantly different distribution patterns with respect to patient age, gender, disease stage, performance status (PS), the presence or absence of systemic B symptoms, the presence or absence of bulky disease, lactic acid dehydrogenase (LDH) levels, and number of extranodal sites (ENS). A significantly greater number of patients in the DLBCL group experienced complete remission (P < 0.0001). Multinomial logistic regression analysis confirmed that immunophenotype, PS, LDH concentration, and number of ENS were independent predictors of response. At a median follow-tip duration of 43 months, there was no observable difference in disease-free Survival (DFS) between patients with DLBCL and patients with PTCL-U; however, multivariate analysis did reveal that poorer PS and bone marrow involvement were significantly associated with shorter DFS. Furthermore, although the overall survival (OS) curves associated with the T-cell and B-cell ummunophenotypes were significantly different from each other at a median follow-up duration of 37 months (P = 0.0012), Cox multivariate analysis excluded immunophenotype from the final OS model. CONCLUSIONS. The findings made in the current study indicate that the natural history of PTCL-U may differ from that of DLBCL. Patients with PTCL-U tended to have less favorable clinical outcomes, although the observed difference in outcome was only partially attributable to immunophenotype, which was independently associated with response, but not with survival. Differences in prognostic factor distributions between patients with PTCL-U and patients with DLBCL may account for some portion of the expected phenotype-associated risk

Calculation of the Aharonov-Bohm wave function

A calculation of the Aharonov-Bohm wave function is presented. The result is a series of confluent hypergeometric functions which is finite at the forward direction.Comment: 12 pages in LaTeX, and 3 PostScript figure

Validation of the international prognostic index in working formulation group a low-grade non-Hodgkin's lymphoma: retrospective analysis of 137 patients from the Gruppo Italiano per lo studio dei linfomi registry.

BACKGROUND AND OBJECTIVE: The subset of non-follicular non-Hodgkin's lymphoma (NHL) includes patients with varied prognoses, thus suitable for different therapeutic approaches. The International Prognostic Index (IPI), originally proposed for aggressive NHL, has been demonstrated to be of prognostic relevance also in follicular NHL. The main aim of the study was to validate the IPI in this histologic category; in addition, the specific prognostic classification, currently employed in the Gruppo Italiano per lo Studio dei Linfomi (GISL) prospective therapeutic trials and based on different features, more similar to those applied to chronic lymphocytic leukemia, was analyzed. DESIGN AND METHODS: The present series consists of 137 evaluable patients affected by Working Formulation group A NHL out of 256 cases referred to the GISL Registry. The retrospective prognostic study included the evaluation by both univariate and multivariate analyses of overall survival, response to therapy and response duration. The IPI was applied as originally proposed. The GISL definition of indolent and aggressive disease at diagnosis was based on the presence of B symptoms, bulky disease, anemia and thrombocytopenia. RESULTS: The distribution of patients in IPI risk groups was rather unbalanced with 18%, 47%, 28% and 7% of cases classified as low (L), intermediate-low (IL), intermediate-high (IH) and high (H) risk, respectively. The median overall survival was not reached in either L or IL risk groups, and was 84.1 and 7.4 months for IH and H risk groups, respectively (p=0. 0005). A simplified IPI model was designed merging patients in both intermediate risk groups and the statistical difference of survival retained its significance. GISL prognostic stratification was demonstrated to have a significant association with survival, with a median survival of 71.3 months in aggressive disease and a median survival not reached at 152 months in indolent disease. Both the simplified IPI model and the GISL risk definition retained their significance in multivariate analysis for overall survival, while for response to therapy only the simplified IPI model resulted to be of statistical significance. In addition, the GISL prognostic stratification identified patients with different outcomes within the IPI intermediate risk group, with a median survival of 70.2 months for patients with aggressive disease wheras the median survival for those with indolent disease was not reached. Finally, a prognostic score resulting from the integration of the simplified IPI and the GISL system was statistically validated. INTERPRETATION AND CONCLUSIONS: The retrospective analysis of this series demonstrates the validity of the IPI in non-follicular indolent NHL and the usefulness of integrating the IPI parameters with disease specific prognostic variables

Prolonged survival in the absence of disease-recurrence in advanced-stage follicular lymphoma following chemo-immunotherapy: 13-year update of the prospective, multicenter randomized GITMO-IIL trial

Aprospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (RHDS) versus conventional chemotherapy with rituximab (CHOP-R) as firstline therapy in 134 high-risk follicular lymphoma patients aged &lt;60 years. The study has been updated at the 13-year median follow up. As of February 2017, 88 (66%) patients were alive, with overall survival of 66.4% at 13 years, without a significant difference between R-HDS (64.5%) and CHOP-R (68.5%). To date, 46 patients have died, mainly because of disease progression (47.8% of all deaths), secondary malignancies (3 solid tumor, 9 myelodysplasia/acute leukemia; 26.1% of all deaths), and other toxicities (21.7% of all deaths). Complete remission was documented in 98 (73.1%) patients and associated with overall survival, with 13- year estimates of 77.0% and 36.8% for complete remission versus no-complete remission, respectively. Molecular remission was documented in 39 (65%) out of 60 evaluable patients and associated with improved survival. In multivariate analysis, complete remission achievement had the strongest effect on survival (P&lt;0.001), along with younger age (P=0.002) and female sex (P=0.013). Overall, 50 patients (37.3%) survived with no disease recurrence (18 CHOP-R, 32 R-HDS). This follow up is the longest reported on follicular lymphoma treated upfront with rituximab-chemotherapy and demonstrates an unprecedented improvement in survival compared to the pre-rituximab era, regardless of the use of intensified or conventional treatment. Complete remission was the most important factor for prolonged survival and a high proportion of patients had prolonged survival in their first remission, raising the issue of curability in follicular lymphoma

On the scattering amplitude in the Aharonov-Bohm gauge field

A general expression for the scattering amplitude of nonrelativistic spinless particles in the Aharonov-Bohm gauge potential is obtained within the time independent formalism. The result is valid also in the backward and forward directions as well as for any choice of the boundary conditions on the wave function at the flux tube position.Comment: 18 pages, plain TE

Quality of life assessment in elderly patients with aggressive non-Hodgkin's Lymphoma treated with anthracycline-containing regimens. Report of a prospective study by the Intergruppo Italiano Linfomi

Background and Objectives. The aim of this study was to evaluate quality of life (QOL) in a group of elderly patients ( > 65 years) with aggressive non-Hodgkin's lymphoma (NHL) treated with chemotherapy regimens containing anthracyclines. Design and Methods. QOL was evaluated in a population of elderly patients with aggressive NHL enrolled in a phase III clinical trial run by the Intergruppo Italiano Linfomi (11L) from 1996 to 1999 to compare two different anthracycline-containing regimens (mini-CEOP vs P-VEBEC). The EORTC-QLQ-C30 questionnaire, which has already been validated in oncology, was used. The questionnaire was administered at the time of diagnosis, half way through the chemotherapy and at the time of restaging. Results. Ninety-one patients completed pre-therapy and post-therapy questionnaires and they are the subject of this report. Baseline QOL assessment showed a strong correlation of poor values of QOL with anemia and high risk according to the International Prognostic Index (IPI). At the end of treatment no functional scales showed worse values. A significant improvement was observed for pain (p = 0.003), appetite (p = 0.006), sleep (p = 0.015) and global health (p = 0.027). Considering only the 50 patients who achieved a complete remission (CR), an improvement was also recorded for emotional state (p = 0.10), role (P = 0.05), constipation (p = 0.04) and global QOL (p = 0.05). Interpretation and Conclusions. The EORTC-QLQ-C30 is feasible even in a population of elderly patients, in whom it had never been tested before. The improvement of QOL at the end of the treatment demonstrated that the symptoms of the disease have a greater negative influence on the patient's life than do the side effects of the therapy